Evidence map›Paper›PMID 29523878›Full record

ArticleGene therapy2018

Improving therapeutic efficacy of IL-12 intratumoral gene electrotransfer through novel plasmid design and modified parameters.

C Burkart, A Mukhopadhyay, S A Shirley, R J Connolly, J H Wright, A Bahrami, J S Campbell, R H Pierce, D A Canton

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.4field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. RecombinantFuture microbiology · 2025
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Intratumoral Plasmid IL12 Expands CD8Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Local Delivery ofCancer research · 2019
    Article
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

C BurkartOncosec Medical Inc., 5820 Nancy Ridge Drive, San Diego, CA, 92121, USA.
A MukhopadhyayOncosec Medical Inc., 5820 Nancy Ridge Drive, San Diego, CA, 92121, USA.
S A ShirleyOncosec Medical Inc., 5820 Nancy Ridge Drive, San Diego, CA, 92121, USA.
R J ConnollyFred Hutchinson Cancer Center, 1100 Fairview Avenue N., Seattle, WA, 98109, USA.
J H WrightOncosec Medical Inc., 5820 Nancy Ridge Drive, San Diego, CA, 92121, USA.
A BahramiOncosec Medical Inc., 5820 Nancy Ridge Drive, San Diego, CA, 92121, USA.
J S CampbellFred Hutchinson Cancer Center, 1100 Fairview Avenue N., Seattle, WA, 98109, USA.
R H PierceFred Hutchinson Cancer Center, 1100 Fairview Avenue N., Seattle, WA, 98109, USA.ORCID http://orcid.org/0000-0002-2677-144X
D A CantonOncosec Medical Inc., 5820 Nancy Ridge Drive, San Diego, CA, 92121, USA. dcanton@oncosec.com.
Fred Hutch Cancer Center · USEden Medical · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The use of immunomodulatory cytokines has been shown effective in regressing a wide range of tumors. However, systemic delivery of recombinant cytokines results in serious, potentially life-threatening, adverse effects. By contrast, nucleic acid transfer via electroporation (EP) is a safe and effective method of delivering plasmid-encoded cytokines to tumors. Intratumoral delivery of IL-12 plasmid DNA by electroporation (IT-pIL12-EP) produced objective response rates in Phase 2 clinical trials in metastatic melanoma. However, only 17.9% of patients receiving IT-pIL12-EP show a complete therapeutic response. Here, we sought to improve the antitumor efficacy of our clinical IT-pIL12-EP plasmid electroporation platform. We evaluated multiple plasmid designs for IL-12 expression. IL-12 expression from a plasmid incorporating a picornavirus-derived co-translational P2A site was the most effective in expressing IL-12p70. In addition, modifying the electroporation parameters improved transfection efficiency and expression of plasmid-derived IL-12p70, as well as its downstream effector IFN-γ in vivo. Finally, using a murine melanoma model that is representative of the intended target patient population, we show that combining modified electroporation conditions with the pIL12-P2A plasmid expression enhances the systemic antitumor response. These improvements to the IT-pIL12-EP platform may improve patient clinical response rates and survival when translated to clinical trials.

Indexed as

Gene Transfer TechniquesPlasmidsAnimalsCD4-CD8 RatioElectroporationEnzyme-Linked Immunosorbent AssayHEK293 CellsHumansInjections, IntralesionalInterferon-gammaInterleukin-12Internal Ribosome Entry SitesMelanoma, ExperimentalMicePicornaviridaeInterferon-gammaInterleukin-12Internal Ribosome Entry Sites

Identifiers

PMID29523878
OpenAlexW2793221955

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.